An Exploration of Subgroups of Mild Cognitive Impairment Based On Cognitive, Neuropsychiatric and Functional Features: Analysis of Data From the National Alzheimer's Coordinating Center

Abstract

Objectives To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups. Design Latent class analysis using 1,655 patients with MCI. Setting Participants in the Uniform Data Set (UDS) from 29 NIH Alzheimer’s Disease Centers. Participants Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination (MMSE) score of 22 or greater. Measurements UDS cognitive battery, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Functional Assessment Questionnaire (FAQ) administered at initial visit. Results Seven empirically-based subgroups of MCI were identified: (1) minimally impaired (relative frequency, 12%); (2) amnestic only (16%); (3) amnestic with functional and neuropsychiatric features (16%); (4) amnestic multi-domain (12%); (5) amnestic multi-domain with functional and neuropsychiatric features (12%); (6) functional and neuropsychiatric features (15%); and (7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score ≥ 4, an indicator of probable CVD. Conclusions Findings suggest there are several distinct phenotypes of MCI characterized by either prominent cognitive features, prominent functional and neuropsychiatric features, or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests there might be distinct differences in disease etiology from the other phenotypes.

Heterogeneous Trajectories of Cognitive Function in Older Adults with Diabetes: Findings from the Korean Longitudinal Study of Aging (KLoSA)

“…The study participants exhibited five distinct cognitive function trajectories: normalmaintained (41.5%), normal-declined (23.8%), mildly impaired-maintained (17.1%), mildly impaired-declined (11.2%), and severely impaired-declined (6.4%). The observed heterogeneity in cognitive function trajectories among older adults with diabetes is consistent with previous study results that identified distinct trajectories in older adults without dementia (Hayden et al, 2011;Hall et al, 2018;Zammit et al, 2018), with MCI (Hanfelt et al, 2011;Xie et al, 2011), and with Alzheimer's disease (Wilkosz et al, 2010;Leoutsakos et al, 2015).…”

Four-year outcome of mild cognitive impairment: The contribution of executive dysfunction.

“…However, even in this case, it has been found that MCI patients with isolated executive impairment were less likely to have underlying AD neuropathology and to be less likely to progress to dementia than those with isolated memory or language impairments (Manly et al, 2008). The limited predictive ability of the EC for subsequent dementia in our study has important implications in light of recent efforts to identify clinically homogeneous MCI subtypes with specific etiology and prognosis (Hanfelt et al, 2011; Johnson et al, 2010). Our results do not support the notion that EC-related MCI subtypes constitute a separate MCI group at increased risk for dementia.…”

Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia

“…Our results may also have implications for understanding the underlying etiology of MCI with NPS. Hanfelt and colleagues (38) found that those MCI phenotypes that showed prominent functional and neuropsychiatric features were more likely to have cerebrovascular disease (CVD) suggesting a possible etiology for MCI with NPS. NPS are likely to be associated with great neurochemical deficits and neuropathology, as we have reviewed recently (39).…”